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快速和中间乙酰化剂在 4,4'-亚甲基双(2-氯苯胺)(MBOCA)暴露工人中对氧化损伤的敏感性较低。

Rapid and intermediate N-acetylators are less susceptible to oxidative damage among 4,4'-methylenebis(2-chloroaniline) (MBOCA)-exposed workers.

机构信息

Department of Family Medicine & Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Neihu, Taipei, Taiwan, ROC.

出版信息

Int J Hyg Environ Health. 2013 Jul;216(4):515-20. doi: 10.1016/j.ijheh.2013.02.001. Epub 2013 Mar 13.

Abstract

OBJECTIVES

In this study, we explored the association between a marker of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG), and genetic polymorphism of the carcinogen-metabolizing enzyme N-acetyltransferase 2 (NAT2) among 4,4'-methylenebis(2-chloroaniline) (MBOCA)-exposed workers.

METHODS

The study population was recruited from four MBOCA-producing factories, and included 57 MBOCA-exposed workers and 101 unexposed control workers. Personal characteristics were collected by questionnaire. Plasma 8-OHdG levels were measured by LC/MS/MS. NAT2 alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP).

RESULTS

NAT2 polymorphism influenced the plasma 8-OHdG levels of MBOCA-exposed workers, but not of non-exposed workers. No difference between exposed and control groups was found for the crude 8-OHdG levels among rapid, intermediate, and slow acetylators. After adjusting for gender, age, smoking, and alcohol consumption habit, the 8-OHdG concentration in the MBOCA-exposed workers was 0.18pg/ml (95% CI -1.80 to -0.12) lower than the control group among rapid and intermediate acetylators. However, the difference between exposed and control groups was not significant for slow acetylators.

CONCLUSION

Gene-environment interactions could play a role in the carcinogenesis of occupational MBOCA exposure. We suggest that the impact of the NAT2 acetylator status is low, if at all, on the generation of the oxidative stress marker 8-OHdG in the investigated exposed group.

摘要

目的

本研究旨在探讨氧化应激标志物 8-羟基脱氧鸟苷(8-OHdG)与接触 4,4'-亚甲基双(2-氯苯胺)(MBOCA)工人中致癌物质代谢酶 N-乙酰转移酶 2(NAT2)遗传多态性之间的关系。

方法

研究人群来自四个 MBOCA 生产工厂,包括 57 名 MBOCA 暴露工人和 101 名未暴露对照工人。通过问卷收集个人特征。通过 LC/MS/MS 测量血浆 8-OHdG 水平。通过聚合酶链反应 - 限制性片段长度多态性(PCR-RFLP)测量 NAT2 等位基因。

结果

NAT2 多态性影响 MBOCA 暴露工人的血浆 8-OHdG 水平,但不影响非暴露工人。在快速、中间和慢乙酰化剂中,暴露组和对照组之间的粗 8-OHdG 水平没有差异。在校正性别、年龄、吸烟和饮酒习惯后,MBOCA 暴露工人的 8-OHdG 浓度比对照组中的快速和中间乙酰化剂低 0.18pg/ml(95%CI-1.80 至-0.12)。然而,对于慢乙酰化剂,暴露组和对照组之间的差异不显著。

结论

基因-环境相互作用可能在职业性 MBOCA 暴露的致癌作用中发挥作用。我们建议,如果有的话,NAT2 乙酰化状态对研究中暴露组氧化应激标志物 8-OHdG 的产生影响很小。

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